The broad objective of this proposal is to understand the physiological processes which regulate the electrical and motor activity of canine and human gastrointestinal smooth muscle. Smooth muscle of the canine gastric sling, fundus, antrum, pylorus, muscularis mucosa, colon and human smooth muscle from normal and diseased stomach and colon will be used. The areas of particular interest are: (1) the voltage-tension relationship which defines the electromechanical coupling characteristics; (2) pattern of intramural motor nerve innervation; (3) the dose-response relationship in single smooth muscle cells for gut peptides (gastrin, cholecystokinin, motilin, somatostatin, substance P, vasoactive intestinal polypeptide and neurotensin) which act directly on the smooth muscle cell and for these which have a neuromodulatory action; (4) the identity of the nonadrenergic, noncholinergic inhibitory transmitter in the muscularis mucosa; and (5) the electrophysiological events responsible for or associated with disturbances in human gastric and colonic motility. The in vitro methods of approach will be the simultaneous measurement of intracellular electrical activity of single smooth muscle cells and motor activity of the muscle, measurement only of motor activity of strips of muscle and radioimmunoassay techniques for identification of the inhibitory transmitter in the muscularis mucosa.